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Internal morphology of ameloblastomas: a study of 24 resected specimens
Internal morphology of ameloblastomas: a study of 24 resected specimens Sizakele P. Ngwenya, BDS,a Erich J. Raubenheimer, MChD, PhD,b and Claudia E. E. Noffke, BChD, MDent,c Medunsa, South Africa UNIVERSITY OF LIMPOPO
Objectives. The objectives of this study were to describe the internal macroscopic architecture of resected specimens of ameloblastoma and to correlate the findings with radiographs and microscopic features. Study design. Resection specimens of 24 ameloblastomas were retrieved from the files of the Department of Oral Pathology at the University of Limpopo. The neoplasms were sectioned in parallel slices and the macroscopic features recorded and each slice was radiographed and sampled for microscopic examination. The macroscopic features were correlated with respective microscopic and radiological appearances. Results. Twenty-three ameloblastomas affected the mandible and 1 the maxilla and measured between 3.3 and 20 cm in greatest diameter. Six cases were unicystic, 2 of which showed incomplete septae both of which presented multilocular on radiographs. Intracystic proliferations were present in 15 cases. These proliferations showed macroscopic features of either small or large nodules with or without the formation of confluent plaques, focal papillary lesions, or multinodular masses that protruded into the cystic cavities. Microscopically these proliferations were characterized by foci of inflammation or plexiform or solid epithelial proliferations, one of which showed a focus of carcinoma in situ, adenomatoid differentiation and another osteodentin deposits. Seven cases had foci of stromal desmoplastic change, one of which exhibited mineralized deposits resembling bone. Conclusions. The assessment of the cystic nature of ameloblastomas on 2-dimensional radiographs is inaccurate. Intraluminal proliferations, in situ carcinomatous change, adenoid differentiation, stromal osteodentin, and bone deposits and desmoplasia were found to be focal rather than generalized phenomena in resection specimen of ameloblastoma. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:754-762)
Ameloblastoma is the most common benign neoplasm of odontogenic epithelial origin. Several clinico-pathologic entities within the spectrum of ameloblastoma have been reported, some of which have prognostic relevance. Peripheral ameloblastomas are rare, occur in periodontal soft tissue, and behave in a hamartomatous fashion unlike their central counterpart, which is neoplastic and locally aggressive. Central or intrabony unicystic (or unilocular) ameloblastomas consist of a single cystic cavity, present generally at a younger age, and are reported to be less aggressive than the multilocular and solid variants.1,2 Histological subtypes of both the unilocular3 and multilocular or solid types4 are well documented. The 3 histological variants of the unicystic ameloblastoma include those with a uniform smooth a
Registrar, Department of Oral Pathology, Medunsa Campus, University of Limpopo, South Africa. b Professor and Head, Department of Oral Pathology, Medunsa Campus, University of Limpopo, South Africa. c Professor and Head, Division of Dentomaxillofacial and Oral Radiology, Medunsa Campus, University of Limpopo, South Africa. Received for publication Nov 21, 2008; returned for revision Jun 23, 2009; accepted for publication Jun 26, 2009. 1079-2104/$ - see front matter © 2009 Published by Mosby, Inc. doi:10.1016/j.tripleo.2009.06.026
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epithelial lining, a nodule of plexiform odontogenic epithelium that protrudes into the cystic space, and a third variety that shows infiltration of the connective tissue wall by typical plexiform or follicular ameloblastomatous epithelium.4 The multilocular and solid types show histologically either follicular or plexiform growth patterns. Not infrequently, both patterns are present in the same tumor. Cellular variants of these 2 main growth patterns are the acanthomatous, granular cell types with the basal cell type being more rare.4 Malignant change either with the microscopic features of a malignant ameloblastoma,5 ameloblastic carcinoma,6-8 or an intraosseous carcinoma9 have been reported in preexisting ameloblastomas. Clear cell differentiation is regarded by some authors to be indicative of low-grade malignant behavior.10 Increased vascularity either as secondary aneurysmal bone cyst change11 or as a hemangiomatous ameloblastoma12 may modify the approach to the surgical removal of the neoplasm. A variant without proven clinical relevance is the desmoplastic ameloblastoma that is characterized by a uniform dense collagenous stroma with small nests and strands of compressed odontogenic epithelium.13,14 Bone deposits within the stroma of an ameloblastoma could contribute to an incorrect radiographic interpretation as an ossifying fibroma.11 Other rare variants include the kera-
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toameloblastoma4 with its papilliferous variant,4,15 as well as ameloblastomas associated with calcifying odontogenic cysts16 or diffuse mineralized dental tissue deposits. The latter is referred to as an odonto-ameloblastoma.17 Focal microscopic differentiation that generally has no clinical meaning have frequently been reported in ameloblastomas. These include mucous cell differentiation,11,18 adenomatoid changes,11,19,20 and an HPV18positive verrucous lesion in a cystic cavity of an ameloblastoma.11 The objectives of this study were to perform a detailed macroscopic description of serial sectioned planes through resected specimens of ameloblastoma and correlate the internal architecture with radiographs and microscopic features. METHODS Twenty-four jaw resections for ameloblastoma received between 2000 and 2004 were retrieved from the laboratory of the Department of Oral Pathology and Oral Biology at the University of Limpopo. Twodimensional preoperative diagnostic radiographs as well as radiographs of the resected specimens were available on all cases. Tumors that involved one jaw quadrant were hemisected along a sagittal plane parallel to the axis of the jaw and those that extended across the midline were hemisected in coronal- or axial planes. Each half was sectioned with a bone saw in 1-cm slices that were prepared parallel to the original sectioned planes. The macroscopic appearances of all surfaces were described, recorded photographically, and compared with 2-dimensional radiographs taken during the diagnostic work-up of the patient and of the resection specimen respectively. The ratio between the solid and cystic parts of the neoplasm as well as the nature and shape of the locules and cystic spaces within each neoplasm were recorded. The solid areas in specimens were regarded as areas in which no macroscopic evidence of cyst formation was present. Cystic change represented the formation of a cavity within the tumor. The terms “unicystic” and “multicystic” were used to describe 1 cyst and 2 or more noninterleading separate cysts within a tumor respectively. The term “multilocular” was used to describe division of a cystic space into locules by incomplete septae or mural ridges. Tissue samples were taken for microscopic examination from areas that were macroscopically distinctive. The microscopic appearances were correlated with the macroscopic features of the site at which the sample was removed. The results were presented in tabular format. RESULTS Demographic data and size and site of the ameloblastomas are reflected in Table I and the radiological,
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Table I. Demographic data Case no.
Age
Gender
Size, cm
Site
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
29 36 31 16 15 24 18 28 34 16 13 21 54 34 Adult 25 76 25 Adult 11 41 Adult 32 34
F F M M M F M M F F F M M M M F M F M F M M F F
11 9 12 7.5 9 6 6 10 16 14 9 11 6 3.3 4 7 14 9.5 11.5 8 5 11 20 18
Left mandible Left maxilla Left & right mandible Left & right mandible Right mandible Right mandible Left mandible Left & right mandible Left & right mandible Left mandible Left mandible Left & right mandible Right mandible Left mandible Left mandible Left mandible Left & right mandible Right mandible Left & right mandible Left & right mandible Left mandible Left & right mandible Left & right mandible Left & right mandible
gross macroscopic, and microscopic features in Table II. Radiographs were generally found to be unreliable in predicting the solid or cystlike nature of an ameloblastoma (Table II, Figs. 1 and 2). Nodular and papillary proliferations in the lumen of one or more cysts were observed in more than half of the cases (Table III). These proliferations correlated microscopically with plexiform or solid epithelial masses (Fig. 3) or foci of inflammation (Fig. 4). Two cases showed areas of pleomorphism and increased mitotic activity in the intraluminal epithelial masses. The presence of a focus of tumor necrosis in one of these prompted a diagnosis of odontogenic carcinoma in situ (Fig. 5). The intraluminal plexiform proliferation of one unicystic ameloblastoma showed adenomatoid differentiation. No ameloblastoma showed uniform desmoplastic change throughout the neoplasm although several cases contained foci of increased fibrous connective tissue that compressed the epithelium in the solid parts of the neoplasm. One predominantly solid ameloblastoma, with a plexiform growth pattern (Case 7), showed an isolated microscopic focus of clear cell differentiation with necrosis and several mitotic figures in the plexiform epithelial strands. Mineralized deposits with the morphology of woven bone were present in focal areas in the solid parts of Case 23. The radiograph showed a mixed radiopaque radiolucent appearance prompting a radiological diagnosis of ossifying fibroma (Fig. 6, A and B). Deposits resembling osteodentin were seen in a focal
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Table II. Radiogrpahic, gross macroscopic, and microscopic appearances Case no. Radologic feature 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Multilocular Multilocular Multilocular Multilocular Multilocular Unilocular Multilocular Multilocular Multilocular Multilocular Multilocular Multilocular Unilocular Unilocular Multilocular Multilocular Multilocular Multilocular Multilocular Multilocular Multilocular Unilocular Multilocular Multilocular
Gross macroscopic features
Microscopic features
Mixed multicystic and solid Mixed multicystic and solid Predominantly solid with a unilocular cyst Multicystic with septae Unicystic with a mural ridge Unicystic without septae or ridges Predominantly solid Predominantly solid with septae Predominantly solid with multiple cysts Predominantly multicystic with septae Predominantly multicystic with septae Predominantly multicystic with septae Unicystic without septae Unicystic without septae or ridges Multicystic and solid with septae Multicystic with septae and solid Predominantly multicystic with septae Predominantly multicystic with septae Predominantly multicystic with septae Mixed multicystic with septae and solid Unicystic with septae Unicystic without septae or ridges Predominantly solid with multiple cysts Predominantly multicystic with septae
Follicular, granular cell differentiation Follicular, acanthomatous differentiation, desmoplasia Plexiform, acanthomatous differentiation Plexiform and follicular, acanthomatous differentiation, desmoplasia Intraluminal plexiform proliferation Intraluminal plexiform proliferation Plexiform, clear cells Follicular, acanthomatous differentiation Follicular, granular cell and acanthomatous differentiation, desmoplasia Plexiform Follicular, desmoplasia Follicular and plexiform Intraluminal and mural proliferation, acanthomatous differentiation Follicular, acanthomatous differentiation Plexiform, acanthomatous and clear cell differentiation, desmoplasia Plexiform, granular cell differentiation Follicular, acanthomatous differentiation Follicular and plexiform, acanthomatous differentiation Follicular, acanthomatous differentiation Plexiform, desmoplasia NOS Mural proliferation Follicular and plexiform, woven bone and desmoplasia Plexiform and follicular, granular cell and acanthomatous differentiation
NOS ⫽ not otherwise specified.
area in the wall of the multilocular cystic space of Case 21. The tumor perforated through the body of the mandible and formed locules that expanded along the buccal and lingual periosteal surfaces (Fig. 7, A and B). DISCUSSION Detailed studies that correlate the macroscopic appearances of sectioned surfaces through ameloblastomas with radiological and microscopic features are conspicuously absent from the literature. The lack of reports in this regard contributes to the general belief that ameloblastomas are, except for the radiological subtyping, based on the locularity of the lesion and microscopic differentiation of the epithelium, generally a homogeneous group of neoplasms. Confirmation of the diagnosis of a resected specimen is therefore often based on random sampling and little attention is given to variations in the macroscopic appearances of sectioned surfaces through a resected tumor. This study investigated correlations among the macroscopic, radiological, and microscopic appearances of 24 ameloblastomas measuring between 3.3 and 20.0 cm in greatest diameter. We demonstrated remarkable morphologic heterogeneity and a poor correlation between 2-dimensional radiographs and the internal macroscopic architecture of the ameloblastomas.
The gross internal macroscopic appearances of 18 resected specimens were polycystic or a mixture of polycystic and solid and 6 were unicystic. This ratio does not reflect accurately on the frequency of unicystic ameloblastomas, as most are treated by curettage and were therefore not included in this study. Conventional 2-dimensional radiographs were found to be inadequate in demonstrating the differences between the solid and cystic areas as well as between incomplete septae and mural ridges (dividing a cyst in locules) or complete septae (resulting in a true multicystic macroscopic appearance). This study, therefore, supports the use of the terms “unilocular” and “multilocular” rather than “unicystic” and “multicystic” to describe the radiological appearances of the internal architecture of an ameloblastoma. A distinction between uni- and multicystic can be made only after macroscopic examination of a resected specimen and these terms should not be used before detailed macroscopic examination of sectioned surfaces of a resected tumor has been executed. The inadequacy of conventional radiographs in illustrating the cystic nature of ameloblastomas is clearly illustrated by Cases 3, 6, and 21 (Figs. 1, 2, and 7). Although Case 3 presented radiologically as a multilocular ameloblastoma, it was mainly solid with one cyst (i.e., unicystic). Cases 6 and 21 presented multilocular
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Fig. 2. Case 6. A, Unicystic ameloblastoma with a mural bony ridge delineated by black arrows (bar ⫽ 1 cm). B, The radiograph showed a multilocular appearance.
Fig. 1. Case 3. A, Predominantly solid ameloblastoma with one unilocular cyst (bar ⫽ 2 cm). B, Preoperative radiograph and (C) radiograph of resection specimen showing a multilocular cystic appearance.
on radiographs but showed one single cystic cavity (unicystic) divided into locules by a mural bony ridge (Case 6) and partial septa (Case 21), which could be identified only by macroscopic examination of the resection specimen. The latter was the result of perforation through the body of the mandible with enlargement of the ameloblastoma along the buccal and lingual periosteal surfaces. The concept of a unicystic multilocular ameloblastoma, as proposed by Reichart et al. in 199521 and questioned by Gardner in 199922 therefore indeed exists. The presence of locules in a cystic space in an ameloblastoma could indicate foci of accelerated growth of the neoplastic lining or an area of reduced resistance of the surrounding tissue to expansion. Irrespective of which mechanism may be valid, we propose that the formation of locules in a cystlike space in a neoplasm generally indicates more active expansion and serves as a radiological feature that warrants a wider excision than would be the case in a smooth contoured unilocular ameloblastoma with a uniform growth rate.
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Table III. Specimens with intraluminal proliferations Case no.
Macroscopic
Microscopic
5 6 8 9 10 12 13 14 15 17 18 20 21 23 24
Multiple small* nodules in one area Small* nodules with microcysts Friable papillary masses in largest cyst Confluent small* nodules, in largest cyst Confluent large† nodules in largest cyst Multiple confluent small nodules in 2 large cysts Multiple small* nodules Multiple small* nodules Coalesced small* nodules forming a plaque in second largest cyst Small* nodules in 2 cysts Small* nodules in several cysts Large† nodules obliterating several cysts Multinodular mass Confluent multinodular mass One small focal papillary lesion
Plexiform proliferation with adenomatoid differentiation Plexiform proliferation Plexiform proliferation with mitosis Plexiform proliferation Plexiform proliferation with focus of carcinoma in situ Plexiform proliferation Inflammation and edema Inflammation with edema Plexiform proliferation Inflammation and edema Plexiform proliferation Plexiform proliferation with foci of desmoplasia Plexiform proliferation with osteodentine Plexiform proliferation Hypercellular with connective tissue cores
*Small: ⱕ 3 mm in diameter. †Large: 4 mm or larger in diameter.
Fig. 3. Intraluminal nodular proliferations with a plexiform ameloblastomatous appearance. A, Multiple coalesced small nodules in one cystic space in Case 15 (arrow; bar ⫽ 1 cm). B, Microscopic appearance of the plexiform arrangement of the odontogenic epithelium (hematoxylin and eosin stain, magnification ⫻40).
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Fig. 4. Intraluminal proliferations associated with inflammation and edema. A, Small nodules in a cyst in Case 17 (bar ⫽ 1 cm). B, Microscopic appearance showing inflammation and edema (hematoxylin and eosin stain, magnification ⫻80).
Foci of mural invasion could not be identified macroscopically in the 2 unicystic ameloblastomas that showed microscopic features of invasion (Cases 13 and 22). It is not feasible to sample the whole wall of a large unicystic ameloblastoma for microscopic examination and the true incidence of mural invasion in unicystic ameloblastomas is probably underestimated. Surgeons are therefore not advised to perform an enucleation after a biopsy failed to show mural invasion and the preferable treatment for all ameloblastomas should be based on excision of small lesions or resection of larger examples with a wide margin of normal tissue, despite contrary recommendations in the literature.23 Macroscopic examination of serial sections through resection specimens of ameloblastomas provided information that was not recorded during examination of the biopsy or original sections obtained through random sampling of the resection specimen. The nodules or papillary masses that projected into the cystic spaces were represented microscopically by epithelium arranged in plexiform or solid arrangements, or were the result of inflammation with edema below the epithelial lining
Fig. 5. Case 10. Intraluminal proliferations with the features of odontogenic carcinoma in situ. A, Multiple confluent large nodules in the largest cyst of the multicystic tumor (ruler in millimeters). B, Microscopic appearance of the nodule indicated by an arrow in A showing pleomorphism and necrosis (hematoxylin and eosin stain, magnification ⫻200).
of the cystic spaces. The origin of the inflammatory change may be related to the initial biopsy procedure that is generally performed several weeks before the surgical resection. The plexiform epithelial proliferations resembled those reported in unicystic ameloblastoma, intraluminal plexiform type.3 Although the smaller nodules were generally separate, those that became larger than 3 mm in diameter demonstrated confluence and formed larger nodular plaques in the wall of the cystic space. A
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Fig. 6. Stromal bone deposits in Case 23. A, Macroscopic appearance of the bone deposits (open arrows, ruler in millimetres). B, Note the bone deposits separated from the neoplastic epithelium (black arrows) by connective tissue (hematoxylin and eosin, magnification ⫻250). C, Mixed radiopaque radiolucent appearance of excision specimen.
unicystic ameloblastoma with small intraluminal nodules showed adenoid differentiation mimicking an adenomatoid odontogenic tumor. Although uncommon, adenoid differentiation in ameloblastomas is a well-described phenomenon.11,19,20 Microscopic changes that mimic those of an adenomatoid odontogenic tumor could compromise an accurate diagnosis on a small incision biopsy, as indeed occurred in the case reported by Evans et al.19 Adenomatoid differentiation is proof of the variability of microscopic expression of neoplastic odontogenic epithelium in an ameloblastoma. Two of the cases with extensive friable papillary masses and large confluent nodules showed foci of pleomorphism and increased mitotic activity (Case 8 and 10). The presence of foci of tumor necrosis in Case 10 prompted a diagnosis of odontogenic carcinoma in situ, as these changes were restricted to a single location in the nodular mass without evidence of invasion beyond the mass. The identification thereof shed a new perspective on the occur-
rence of early malignant change in ameloblastomas. Both cases were multicystic and measured 10 cm or more in diameter, indicating that foci of malignant change within a cystic ameloblastoma are more likely to occur in large multicystic tumors and may present as confluent papillary or nodular masses that protrude into a cystic space. One case in our series (Case 7) showed a focus of clear cell differentiation in the solid part of the neoplasm. The distinction between a clear cell–type ameloblastoma and clear cell odontogenic carcinoma is extremely difficult, to the extent that Braunstein et al. in their recent review10 regard both lesions as low-grade malignancies on a clinico-pathologic continuum of a single disease entity rather than 2 separate lesions. Maiorano et al.24 recommended that terms such as clear cell ameloblastoma and clear cell odontogenic tumor not be used because of the unpredictable behavior of such tumors. Multiple histological samples from our
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Fig. 7. Case 21. A, Cropped panoramic radiograph showing the multilocular radiologic appearance. B, Axial section inferior to the roots of the teeth through the unicystic cavity of Case 21 shows perforation of the mandible with buccal (bottom of picture) and lingual (top of picture) expansion. Enlargement created locules (asterisks) on the buccal and lingual surfaces of the body of the mandible. The arrow indicates a focal deposit of osteodentine in the capsule of the tumor on the perforated edge of the mandible.
cases with clear cell differentiation (Cases 7 and 15) revealed clear cells in one locality only and the outline of the groups of clear cells did not deviate from the plexiform growth patterns of the remainder of the neoplasms. Mitotic activity and tumor necrosis was found in the clear cell area in Case 7. Labeling the neoplasm as malignant would lead to aggressive management to the detriment of the patient. It is probably appropriate to refer to focal clear cell change with necrosis within an otherwise classic ameloblastoma as an area of clear cell carcinoma in situ until follow-up studies guide us otherwise. The confluent multinodular mass in Case 21 demonstrated plexiform epithelial proliferation associ-
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ated with the depositioning of dental hard tissue. The focal deposits of osteodentin did not warrant a diagnosis of ameloblastic fibrodentinoma, as a concomitant ectomesenchymal proliferation was absent and therefore did not conform to the World Health Organization definition of an ameloblastic fibrodentinoma.4 The formation of dental hard tissue was probably the result of a retained inductive capacity of a focal group of neoplastic ameloblasts and ectomesenchyme in the neoplasm. Focal proliferation of fibrous connective tissue seen in 7 cases could also be ascribed to mesenchymal induction mediated by neoplastic ameloblasts. None of the ameloblastomas showed a uniform proliferation of connective tissue that compressed the epithelium in small nests and strands throughout the neoplasm. A diagnosis of a desmoplastic ameloblastoma was not applied to any of the specimens that showed focal desmoplastic change. Care should be taken when interpreting reports on desmoplastic ameloblastomas whether the desmoplastic change is focal or generalized throughout the tumor, as the focal variety appears to be common and should not be accepted as a criterion for the diagnosis of a desmoplastic ameloblastoma. Attempts to subdivide ameloblastomas in desmoplastic, hybrid, and infiltrative (nondesmoplastic) types based on the uniformity of the stromal fibrous reaction25 should be discouraged, as no report as yet could prove any difference in their biologic behavior among these groups. The extensive formation of bone in the fibrous connective tissue stroma in Case 23 was an interesting phenomenon. This process was more likely the result of bony metaplasia of the fibrous connective tissue rather than direct induction by the odontogenic epithelium as the bone was separated from the neoplastic epithelial islands by mature connective tissue. Alternatively it could represent a manifestation of the rare albeit well documented association between ameloblastomas with desmoplasia and concomitant fibro-osseous lesions.26 This phenomenon could precipitate an incorrect radiological diagnosis of ossifying fibroma. In conclusion, this study demonstrated that an accurate description of the nature of the cystic and solid areas in an ameloblastoma is beyond the capability of conventional 2-dimensional radiographs and can be done only with thorough examination of the resection specimen. Our findings show that radiologically unilocular ameloblastomas are generally unicystic with macroscopic examination. Ameloblastomas with a radiological multilocular appearance on the other hand may be unicystic, multicystic, solid, or a combination of these possibilities with macroscopic examination. Surgeons should be advised not to treat unilocular ameloblastomas different to their multilocular counterparts because of the nonrepresentative nature of an incision
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biopsy and the unlikelihood that it would demonstrate a focus of mural invasion if present. Thorough macroscopic examination of a resection specimen is important to identify intracystic proliferations that may represent a focus of malignant change, especially in large multicystic ameloblastomas. The tendency in the literature to use clinically irrelevant microscopic features to subclassify ameloblastomas into subtypes should be discouraged. The addition of irrelevant prefixes like “adenoid,”20 “desmoplastic,”25 or “desmoplastic hybrid”26 to a diagnosis of an ameloblastoma serves no purpose but to confuse clinicians. REFERENCES 1. Rapidis AD, Andressakis DD, Stavrianos SD, Faratzis G, Arnogiannaki-Liappi N, Lagogiannis GA, et al. Ameloblastomas of the jaws: clinico-pathological review of 11 patients. Eur J Surg Oncol 2004;30(9):998-1002. 2. Nakamura N, Mitsunyasu T, Highuchi Y, Sandra F, Ohisi M. Growth characteristics of ameloblastoma involving the inferior alveolar nerve: a clinical and histopathologic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91(5): 557-66. 3. Ackerman GL, Altini M, Shear M. The unicystic ameloblastoma: a clinico-pathological study of 57 cases. J Oral Pathol 1988;17:541-6. 4. Kramer IRH, Pindborg JJ, Shear M. Histological typing of odontogenic tumors. Berlin: Springer Verlag; 1992. p. 11-4. 5. Zarbo RJ, Marunick MT, Johns R. Malignant ameloblastoma, spindle cell variant. Arch Pathol Lab Med 2003;127(3):352-5. 6. Dhir K, Scuibba J, Tufano RP. Ameloblastic carcinoma of the maxilla. Oral Oncol 2003;39(7):736-41. 7. Avon SL, Mccomb J, Clokie C. Ameloblastic carcinoma: case report and literature review. J Can Dent Assoc 2003;69(9):573-6. 8. Cox DP, Muller S, Carlson GW, Murray D. Ameloblastic carcinoma ex ameloblastoma of the mandible with malignancy-associated hypercalcemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90(6):716-22. 9. Hamakawa H, Kayahara H, Sumida T, Tanioka H. Mandibular intraosseous carcinoma coexisting with ameloblastoma. J Oral Maxillofac Surg 2000;58(4):430-3. 10. Braunstein E, Vered M, Taicher S, Buchner A. Clear cell odontogenic carcinoma and clear cell ameloblastoma: a single clinicopathologic entity? A new case and comparative analysis of the literature. J Oral Maxillofac Surg 2003;61(9):1004-10. 11. Raubenheimer EJ, Van Heerden WFP, Noffke CEE. Infrequent clinicopathological findings in 108 ameloblastomas. J Oral Pathol Med 1995;24:227-32. 12. Van Rensburg LJ, Thompson IO, Kruger HE, Norval EJ. Hemangiomatous ameloblastoma: clinical, radiologic, and patho-
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logic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91(3):374-80. Durmus E, Kalayici A, Ozturk A, Gunham O. Desmoplastic ameloblastoma of the mandible. J Craniofac Surg 2003;14(6):873-5. Kishino M, Murakami S, Fukada Y, Ishida T. Pathology of the desmoplastic ameloblastoma. J Oral Pathol Med 2001;30(1):35-40. Collini P, Zucchini N, Vessechia G, Guzzo M. Papilliferous keratoameloblastoma of the mandible: a papillary ameloblastic carcinoma: report of a case with a 6-year follow-up and review of the literature. Int J Oral Surg 2002;10(2):149-55. Iida S, Ueda T, Aikawa T, Koshino M, Okura M, Kogo M. Ameloblastomatous calcifying odontogenic cyst in the mandible. Dentomaxillofac Radiol 2004;33(6):409-12. Mosqueda-Taylor A, Carlos-Bregni R, Ramirez-Amador V, PalmaGuzman JM, Esquivel-Bonilla D, Hernandez-Rojase LA. Odontoameloblastoma. Clinico-pathologic study of three cases and critical review of the literature. Oral Oncol 2002;38(8):800-5. Wilson D, Walker M, Aurora N, Moore S. Ameloblastoma with mucous cell differentiation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91(5):576-8. Evans BL, Carr RF, Phillipe LJ. Adenoid ameloblastoma with dentinoid: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;98(5):583-8. Matsumoto Y, Mizoue K, Seto K. Atypical plexiform ameloblastoma with dentinoid: adenoid ameloblastoma with dentinoid. J Oral Pathol Med 2001;30(4):251-4. Reichart PA, Philipsen HP, Sonner S. Ameloblastoma: biological profile of 3677 cases. Eur J Cancer B Oral Oncol 1995;31B(2):86-99. Gardner DG. Critique of the 1995 review by Reichart et al. of the biological profile of 3677 ameloblastomas. Oral Oncol 1999;35(4):443-9. Philipsen HP, Reichart PA. Unicystic ameloblastoma. A review of 193 cases from the literature. Oral Oncol 1998;34(5):17-25. Maiorano E, Altini M, Viale G, Piatelli A, Favia G. Clear cell odontogenic carcinoma. Report of two cases and review of the literature. Am J Clin Pathol 2001;116(1):107-14. Philipsen HP, Reichart PA, Takata T. Desmoplastic ameloblastoma (including “hybrid” lesion of ameloblastoma). Biological profile based on 100 cases from the literature and own files. Oral Oncol 2001;37(5):455-60. Wakoh M, Harada T, Inuoe T. Follicular/desmoplastic hybrid ameloblastoma with radiographic features of concomitant fibroosseous and solitary cystic lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94(6):774-80.
Reprint requests: Erich J. Raubenheimer, MChD, PhD Department of Oral Pathology University of Limpopo Box D24 Medunsa, 0204, South Africa [email protected]
Objectives. The objectives of this study were to describe the internal macroscopic architecture of resected specimens of ameloblastoma and to correlate the findings with radiographs and microscopic features. Study design. Resection specimens of 24 ameloblastomas were retrieved from the files of the Department of Oral Pathology at the University of Limpopo. The neoplasms were sectioned in parallel slices and the macroscopic features recorded and each slice was radiographed and sampled for microscopic examination. The macroscopic features were correlated with respective microscopic and radiological appearances. Results. Twenty-three ameloblastomas affected the mandible and 1 the maxilla and measured between 3.3 and 20 cm in greatest diameter. Six cases were unicystic, 2 of which showed incomplete septae both of which presented multilocular on radiographs. Intracystic proliferations were present in 15 cases. These proliferations showed macroscopic features of either small or large nodules with or without the formation of confluent plaques, focal papillary lesions, or multinodular masses that protruded into the cystic cavities. Microscopically these proliferations were characterized by foci of inflammation or plexiform or solid epithelial proliferations, one of which showed a focus of carcinoma in situ, adenomatoid differentiation and another osteodentin deposits. Seven cases had foci of stromal desmoplastic change, one of which exhibited mineralized deposits resembling bone. Conclusions. The assessment of the cystic nature of ameloblastomas on 2-dimensional radiographs is inaccurate. Intraluminal proliferations, in situ carcinomatous change, adenoid differentiation, stromal osteodentin, and bone deposits and desmoplasia were found to be focal rather than generalized phenomena in resection specimen of ameloblastoma. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:754-762)
Ameloblastoma is the most common benign neoplasm of odontogenic epithelial origin. Several clinico-pathologic entities within the spectrum of ameloblastoma have been reported, some of which have prognostic relevance. Peripheral ameloblastomas are rare, occur in periodontal soft tissue, and behave in a hamartomatous fashion unlike their central counterpart, which is neoplastic and locally aggressive. Central or intrabony unicystic (or unilocular) ameloblastomas consist of a single cystic cavity, present generally at a younger age, and are reported to be less aggressive than the multilocular and solid variants.1,2 Histological subtypes of both the unilocular3 and multilocular or solid types4 are well documented. The 3 histological variants of the unicystic ameloblastoma include those with a uniform smooth a
Registrar, Department of Oral Pathology, Medunsa Campus, University of Limpopo, South Africa. b Professor and Head, Department of Oral Pathology, Medunsa Campus, University of Limpopo, South Africa. c Professor and Head, Division of Dentomaxillofacial and Oral Radiology, Medunsa Campus, University of Limpopo, South Africa. Received for publication Nov 21, 2008; returned for revision Jun 23, 2009; accepted for publication Jun 26, 2009. 1079-2104/$ - see front matter © 2009 Published by Mosby, Inc. doi:10.1016/j.tripleo.2009.06.026
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epithelial lining, a nodule of plexiform odontogenic epithelium that protrudes into the cystic space, and a third variety that shows infiltration of the connective tissue wall by typical plexiform or follicular ameloblastomatous epithelium.4 The multilocular and solid types show histologically either follicular or plexiform growth patterns. Not infrequently, both patterns are present in the same tumor. Cellular variants of these 2 main growth patterns are the acanthomatous, granular cell types with the basal cell type being more rare.4 Malignant change either with the microscopic features of a malignant ameloblastoma,5 ameloblastic carcinoma,6-8 or an intraosseous carcinoma9 have been reported in preexisting ameloblastomas. Clear cell differentiation is regarded by some authors to be indicative of low-grade malignant behavior.10 Increased vascularity either as secondary aneurysmal bone cyst change11 or as a hemangiomatous ameloblastoma12 may modify the approach to the surgical removal of the neoplasm. A variant without proven clinical relevance is the desmoplastic ameloblastoma that is characterized by a uniform dense collagenous stroma with small nests and strands of compressed odontogenic epithelium.13,14 Bone deposits within the stroma of an ameloblastoma could contribute to an incorrect radiographic interpretation as an ossifying fibroma.11 Other rare variants include the kera-
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toameloblastoma4 with its papilliferous variant,4,15 as well as ameloblastomas associated with calcifying odontogenic cysts16 or diffuse mineralized dental tissue deposits. The latter is referred to as an odonto-ameloblastoma.17 Focal microscopic differentiation that generally has no clinical meaning have frequently been reported in ameloblastomas. These include mucous cell differentiation,11,18 adenomatoid changes,11,19,20 and an HPV18positive verrucous lesion in a cystic cavity of an ameloblastoma.11 The objectives of this study were to perform a detailed macroscopic description of serial sectioned planes through resected specimens of ameloblastoma and correlate the internal architecture with radiographs and microscopic features. METHODS Twenty-four jaw resections for ameloblastoma received between 2000 and 2004 were retrieved from the laboratory of the Department of Oral Pathology and Oral Biology at the University of Limpopo. Twodimensional preoperative diagnostic radiographs as well as radiographs of the resected specimens were available on all cases. Tumors that involved one jaw quadrant were hemisected along a sagittal plane parallel to the axis of the jaw and those that extended across the midline were hemisected in coronal- or axial planes. Each half was sectioned with a bone saw in 1-cm slices that were prepared parallel to the original sectioned planes. The macroscopic appearances of all surfaces were described, recorded photographically, and compared with 2-dimensional radiographs taken during the diagnostic work-up of the patient and of the resection specimen respectively. The ratio between the solid and cystic parts of the neoplasm as well as the nature and shape of the locules and cystic spaces within each neoplasm were recorded. The solid areas in specimens were regarded as areas in which no macroscopic evidence of cyst formation was present. Cystic change represented the formation of a cavity within the tumor. The terms “unicystic” and “multicystic” were used to describe 1 cyst and 2 or more noninterleading separate cysts within a tumor respectively. The term “multilocular” was used to describe division of a cystic space into locules by incomplete septae or mural ridges. Tissue samples were taken for microscopic examination from areas that were macroscopically distinctive. The microscopic appearances were correlated with the macroscopic features of the site at which the sample was removed. The results were presented in tabular format. RESULTS Demographic data and size and site of the ameloblastomas are reflected in Table I and the radiological,
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Table I. Demographic data Case no.
Age
Gender
Size, cm
Site
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
29 36 31 16 15 24 18 28 34 16 13 21 54 34 Adult 25 76 25 Adult 11 41 Adult 32 34
F F M M M F M M F F F M M M M F M F M F M M F F
11 9 12 7.5 9 6 6 10 16 14 9 11 6 3.3 4 7 14 9.5 11.5 8 5 11 20 18
Left mandible Left maxilla Left & right mandible Left & right mandible Right mandible Right mandible Left mandible Left & right mandible Left & right mandible Left mandible Left mandible Left & right mandible Right mandible Left mandible Left mandible Left mandible Left & right mandible Right mandible Left & right mandible Left & right mandible Left mandible Left & right mandible Left & right mandible Left & right mandible
gross macroscopic, and microscopic features in Table II. Radiographs were generally found to be unreliable in predicting the solid or cystlike nature of an ameloblastoma (Table II, Figs. 1 and 2). Nodular and papillary proliferations in the lumen of one or more cysts were observed in more than half of the cases (Table III). These proliferations correlated microscopically with plexiform or solid epithelial masses (Fig. 3) or foci of inflammation (Fig. 4). Two cases showed areas of pleomorphism and increased mitotic activity in the intraluminal epithelial masses. The presence of a focus of tumor necrosis in one of these prompted a diagnosis of odontogenic carcinoma in situ (Fig. 5). The intraluminal plexiform proliferation of one unicystic ameloblastoma showed adenomatoid differentiation. No ameloblastoma showed uniform desmoplastic change throughout the neoplasm although several cases contained foci of increased fibrous connective tissue that compressed the epithelium in the solid parts of the neoplasm. One predominantly solid ameloblastoma, with a plexiform growth pattern (Case 7), showed an isolated microscopic focus of clear cell differentiation with necrosis and several mitotic figures in the plexiform epithelial strands. Mineralized deposits with the morphology of woven bone were present in focal areas in the solid parts of Case 23. The radiograph showed a mixed radiopaque radiolucent appearance prompting a radiological diagnosis of ossifying fibroma (Fig. 6, A and B). Deposits resembling osteodentin were seen in a focal
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Table II. Radiogrpahic, gross macroscopic, and microscopic appearances Case no. Radologic feature 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Multilocular Multilocular Multilocular Multilocular Multilocular Unilocular Multilocular Multilocular Multilocular Multilocular Multilocular Multilocular Unilocular Unilocular Multilocular Multilocular Multilocular Multilocular Multilocular Multilocular Multilocular Unilocular Multilocular Multilocular
Gross macroscopic features
Microscopic features
Mixed multicystic and solid Mixed multicystic and solid Predominantly solid with a unilocular cyst Multicystic with septae Unicystic with a mural ridge Unicystic without septae or ridges Predominantly solid Predominantly solid with septae Predominantly solid with multiple cysts Predominantly multicystic with septae Predominantly multicystic with septae Predominantly multicystic with septae Unicystic without septae Unicystic without septae or ridges Multicystic and solid with septae Multicystic with septae and solid Predominantly multicystic with septae Predominantly multicystic with septae Predominantly multicystic with septae Mixed multicystic with septae and solid Unicystic with septae Unicystic without septae or ridges Predominantly solid with multiple cysts Predominantly multicystic with septae
Follicular, granular cell differentiation Follicular, acanthomatous differentiation, desmoplasia Plexiform, acanthomatous differentiation Plexiform and follicular, acanthomatous differentiation, desmoplasia Intraluminal plexiform proliferation Intraluminal plexiform proliferation Plexiform, clear cells Follicular, acanthomatous differentiation Follicular, granular cell and acanthomatous differentiation, desmoplasia Plexiform Follicular, desmoplasia Follicular and plexiform Intraluminal and mural proliferation, acanthomatous differentiation Follicular, acanthomatous differentiation Plexiform, acanthomatous and clear cell differentiation, desmoplasia Plexiform, granular cell differentiation Follicular, acanthomatous differentiation Follicular and plexiform, acanthomatous differentiation Follicular, acanthomatous differentiation Plexiform, desmoplasia NOS Mural proliferation Follicular and plexiform, woven bone and desmoplasia Plexiform and follicular, granular cell and acanthomatous differentiation
NOS ⫽ not otherwise specified.
area in the wall of the multilocular cystic space of Case 21. The tumor perforated through the body of the mandible and formed locules that expanded along the buccal and lingual periosteal surfaces (Fig. 7, A and B). DISCUSSION Detailed studies that correlate the macroscopic appearances of sectioned surfaces through ameloblastomas with radiological and microscopic features are conspicuously absent from the literature. The lack of reports in this regard contributes to the general belief that ameloblastomas are, except for the radiological subtyping, based on the locularity of the lesion and microscopic differentiation of the epithelium, generally a homogeneous group of neoplasms. Confirmation of the diagnosis of a resected specimen is therefore often based on random sampling and little attention is given to variations in the macroscopic appearances of sectioned surfaces through a resected tumor. This study investigated correlations among the macroscopic, radiological, and microscopic appearances of 24 ameloblastomas measuring between 3.3 and 20.0 cm in greatest diameter. We demonstrated remarkable morphologic heterogeneity and a poor correlation between 2-dimensional radiographs and the internal macroscopic architecture of the ameloblastomas.
The gross internal macroscopic appearances of 18 resected specimens were polycystic or a mixture of polycystic and solid and 6 were unicystic. This ratio does not reflect accurately on the frequency of unicystic ameloblastomas, as most are treated by curettage and were therefore not included in this study. Conventional 2-dimensional radiographs were found to be inadequate in demonstrating the differences between the solid and cystic areas as well as between incomplete septae and mural ridges (dividing a cyst in locules) or complete septae (resulting in a true multicystic macroscopic appearance). This study, therefore, supports the use of the terms “unilocular” and “multilocular” rather than “unicystic” and “multicystic” to describe the radiological appearances of the internal architecture of an ameloblastoma. A distinction between uni- and multicystic can be made only after macroscopic examination of a resected specimen and these terms should not be used before detailed macroscopic examination of sectioned surfaces of a resected tumor has been executed. The inadequacy of conventional radiographs in illustrating the cystic nature of ameloblastomas is clearly illustrated by Cases 3, 6, and 21 (Figs. 1, 2, and 7). Although Case 3 presented radiologically as a multilocular ameloblastoma, it was mainly solid with one cyst (i.e., unicystic). Cases 6 and 21 presented multilocular
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Fig. 2. Case 6. A, Unicystic ameloblastoma with a mural bony ridge delineated by black arrows (bar ⫽ 1 cm). B, The radiograph showed a multilocular appearance.
Fig. 1. Case 3. A, Predominantly solid ameloblastoma with one unilocular cyst (bar ⫽ 2 cm). B, Preoperative radiograph and (C) radiograph of resection specimen showing a multilocular cystic appearance.
on radiographs but showed one single cystic cavity (unicystic) divided into locules by a mural bony ridge (Case 6) and partial septa (Case 21), which could be identified only by macroscopic examination of the resection specimen. The latter was the result of perforation through the body of the mandible with enlargement of the ameloblastoma along the buccal and lingual periosteal surfaces. The concept of a unicystic multilocular ameloblastoma, as proposed by Reichart et al. in 199521 and questioned by Gardner in 199922 therefore indeed exists. The presence of locules in a cystic space in an ameloblastoma could indicate foci of accelerated growth of the neoplastic lining or an area of reduced resistance of the surrounding tissue to expansion. Irrespective of which mechanism may be valid, we propose that the formation of locules in a cystlike space in a neoplasm generally indicates more active expansion and serves as a radiological feature that warrants a wider excision than would be the case in a smooth contoured unilocular ameloblastoma with a uniform growth rate.
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Table III. Specimens with intraluminal proliferations Case no.
Macroscopic
Microscopic
5 6 8 9 10 12 13 14 15 17 18 20 21 23 24
Multiple small* nodules in one area Small* nodules with microcysts Friable papillary masses in largest cyst Confluent small* nodules, in largest cyst Confluent large† nodules in largest cyst Multiple confluent small nodules in 2 large cysts Multiple small* nodules Multiple small* nodules Coalesced small* nodules forming a plaque in second largest cyst Small* nodules in 2 cysts Small* nodules in several cysts Large† nodules obliterating several cysts Multinodular mass Confluent multinodular mass One small focal papillary lesion
Plexiform proliferation with adenomatoid differentiation Plexiform proliferation Plexiform proliferation with mitosis Plexiform proliferation Plexiform proliferation with focus of carcinoma in situ Plexiform proliferation Inflammation and edema Inflammation with edema Plexiform proliferation Inflammation and edema Plexiform proliferation Plexiform proliferation with foci of desmoplasia Plexiform proliferation with osteodentine Plexiform proliferation Hypercellular with connective tissue cores
*Small: ⱕ 3 mm in diameter. †Large: 4 mm or larger in diameter.
Fig. 3. Intraluminal nodular proliferations with a plexiform ameloblastomatous appearance. A, Multiple coalesced small nodules in one cystic space in Case 15 (arrow; bar ⫽ 1 cm). B, Microscopic appearance of the plexiform arrangement of the odontogenic epithelium (hematoxylin and eosin stain, magnification ⫻40).
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Fig. 4. Intraluminal proliferations associated with inflammation and edema. A, Small nodules in a cyst in Case 17 (bar ⫽ 1 cm). B, Microscopic appearance showing inflammation and edema (hematoxylin and eosin stain, magnification ⫻80).
Foci of mural invasion could not be identified macroscopically in the 2 unicystic ameloblastomas that showed microscopic features of invasion (Cases 13 and 22). It is not feasible to sample the whole wall of a large unicystic ameloblastoma for microscopic examination and the true incidence of mural invasion in unicystic ameloblastomas is probably underestimated. Surgeons are therefore not advised to perform an enucleation after a biopsy failed to show mural invasion and the preferable treatment for all ameloblastomas should be based on excision of small lesions or resection of larger examples with a wide margin of normal tissue, despite contrary recommendations in the literature.23 Macroscopic examination of serial sections through resection specimens of ameloblastomas provided information that was not recorded during examination of the biopsy or original sections obtained through random sampling of the resection specimen. The nodules or papillary masses that projected into the cystic spaces were represented microscopically by epithelium arranged in plexiform or solid arrangements, or were the result of inflammation with edema below the epithelial lining
Fig. 5. Case 10. Intraluminal proliferations with the features of odontogenic carcinoma in situ. A, Multiple confluent large nodules in the largest cyst of the multicystic tumor (ruler in millimeters). B, Microscopic appearance of the nodule indicated by an arrow in A showing pleomorphism and necrosis (hematoxylin and eosin stain, magnification ⫻200).
of the cystic spaces. The origin of the inflammatory change may be related to the initial biopsy procedure that is generally performed several weeks before the surgical resection. The plexiform epithelial proliferations resembled those reported in unicystic ameloblastoma, intraluminal plexiform type.3 Although the smaller nodules were generally separate, those that became larger than 3 mm in diameter demonstrated confluence and formed larger nodular plaques in the wall of the cystic space. A
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Fig. 6. Stromal bone deposits in Case 23. A, Macroscopic appearance of the bone deposits (open arrows, ruler in millimetres). B, Note the bone deposits separated from the neoplastic epithelium (black arrows) by connective tissue (hematoxylin and eosin, magnification ⫻250). C, Mixed radiopaque radiolucent appearance of excision specimen.
unicystic ameloblastoma with small intraluminal nodules showed adenoid differentiation mimicking an adenomatoid odontogenic tumor. Although uncommon, adenoid differentiation in ameloblastomas is a well-described phenomenon.11,19,20 Microscopic changes that mimic those of an adenomatoid odontogenic tumor could compromise an accurate diagnosis on a small incision biopsy, as indeed occurred in the case reported by Evans et al.19 Adenomatoid differentiation is proof of the variability of microscopic expression of neoplastic odontogenic epithelium in an ameloblastoma. Two of the cases with extensive friable papillary masses and large confluent nodules showed foci of pleomorphism and increased mitotic activity (Case 8 and 10). The presence of foci of tumor necrosis in Case 10 prompted a diagnosis of odontogenic carcinoma in situ, as these changes were restricted to a single location in the nodular mass without evidence of invasion beyond the mass. The identification thereof shed a new perspective on the occur-
rence of early malignant change in ameloblastomas. Both cases were multicystic and measured 10 cm or more in diameter, indicating that foci of malignant change within a cystic ameloblastoma are more likely to occur in large multicystic tumors and may present as confluent papillary or nodular masses that protrude into a cystic space. One case in our series (Case 7) showed a focus of clear cell differentiation in the solid part of the neoplasm. The distinction between a clear cell–type ameloblastoma and clear cell odontogenic carcinoma is extremely difficult, to the extent that Braunstein et al. in their recent review10 regard both lesions as low-grade malignancies on a clinico-pathologic continuum of a single disease entity rather than 2 separate lesions. Maiorano et al.24 recommended that terms such as clear cell ameloblastoma and clear cell odontogenic tumor not be used because of the unpredictable behavior of such tumors. Multiple histological samples from our
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Fig. 7. Case 21. A, Cropped panoramic radiograph showing the multilocular radiologic appearance. B, Axial section inferior to the roots of the teeth through the unicystic cavity of Case 21 shows perforation of the mandible with buccal (bottom of picture) and lingual (top of picture) expansion. Enlargement created locules (asterisks) on the buccal and lingual surfaces of the body of the mandible. The arrow indicates a focal deposit of osteodentine in the capsule of the tumor on the perforated edge of the mandible.
cases with clear cell differentiation (Cases 7 and 15) revealed clear cells in one locality only and the outline of the groups of clear cells did not deviate from the plexiform growth patterns of the remainder of the neoplasms. Mitotic activity and tumor necrosis was found in the clear cell area in Case 7. Labeling the neoplasm as malignant would lead to aggressive management to the detriment of the patient. It is probably appropriate to refer to focal clear cell change with necrosis within an otherwise classic ameloblastoma as an area of clear cell carcinoma in situ until follow-up studies guide us otherwise. The confluent multinodular mass in Case 21 demonstrated plexiform epithelial proliferation associ-
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ated with the depositioning of dental hard tissue. The focal deposits of osteodentin did not warrant a diagnosis of ameloblastic fibrodentinoma, as a concomitant ectomesenchymal proliferation was absent and therefore did not conform to the World Health Organization definition of an ameloblastic fibrodentinoma.4 The formation of dental hard tissue was probably the result of a retained inductive capacity of a focal group of neoplastic ameloblasts and ectomesenchyme in the neoplasm. Focal proliferation of fibrous connective tissue seen in 7 cases could also be ascribed to mesenchymal induction mediated by neoplastic ameloblasts. None of the ameloblastomas showed a uniform proliferation of connective tissue that compressed the epithelium in small nests and strands throughout the neoplasm. A diagnosis of a desmoplastic ameloblastoma was not applied to any of the specimens that showed focal desmoplastic change. Care should be taken when interpreting reports on desmoplastic ameloblastomas whether the desmoplastic change is focal or generalized throughout the tumor, as the focal variety appears to be common and should not be accepted as a criterion for the diagnosis of a desmoplastic ameloblastoma. Attempts to subdivide ameloblastomas in desmoplastic, hybrid, and infiltrative (nondesmoplastic) types based on the uniformity of the stromal fibrous reaction25 should be discouraged, as no report as yet could prove any difference in their biologic behavior among these groups. The extensive formation of bone in the fibrous connective tissue stroma in Case 23 was an interesting phenomenon. This process was more likely the result of bony metaplasia of the fibrous connective tissue rather than direct induction by the odontogenic epithelium as the bone was separated from the neoplastic epithelial islands by mature connective tissue. Alternatively it could represent a manifestation of the rare albeit well documented association between ameloblastomas with desmoplasia and concomitant fibro-osseous lesions.26 This phenomenon could precipitate an incorrect radiological diagnosis of ossifying fibroma. In conclusion, this study demonstrated that an accurate description of the nature of the cystic and solid areas in an ameloblastoma is beyond the capability of conventional 2-dimensional radiographs and can be done only with thorough examination of the resection specimen. Our findings show that radiologically unilocular ameloblastomas are generally unicystic with macroscopic examination. Ameloblastomas with a radiological multilocular appearance on the other hand may be unicystic, multicystic, solid, or a combination of these possibilities with macroscopic examination. Surgeons should be advised not to treat unilocular ameloblastomas different to their multilocular counterparts because of the nonrepresentative nature of an incision
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biopsy and the unlikelihood that it would demonstrate a focus of mural invasion if present. Thorough macroscopic examination of a resection specimen is important to identify intracystic proliferations that may represent a focus of malignant change, especially in large multicystic ameloblastomas. The tendency in the literature to use clinically irrelevant microscopic features to subclassify ameloblastomas into subtypes should be discouraged. The addition of irrelevant prefixes like “adenoid,”20 “desmoplastic,”25 or “desmoplastic hybrid”26 to a diagnosis of an ameloblastoma serves no purpose but to confuse clinicians. REFERENCES 1. Rapidis AD, Andressakis DD, Stavrianos SD, Faratzis G, Arnogiannaki-Liappi N, Lagogiannis GA, et al. Ameloblastomas of the jaws: clinico-pathological review of 11 patients. Eur J Surg Oncol 2004;30(9):998-1002. 2. Nakamura N, Mitsunyasu T, Highuchi Y, Sandra F, Ohisi M. Growth characteristics of ameloblastoma involving the inferior alveolar nerve: a clinical and histopathologic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91(5): 557-66. 3. Ackerman GL, Altini M, Shear M. The unicystic ameloblastoma: a clinico-pathological study of 57 cases. J Oral Pathol 1988;17:541-6. 4. Kramer IRH, Pindborg JJ, Shear M. Histological typing of odontogenic tumors. Berlin: Springer Verlag; 1992. p. 11-4. 5. Zarbo RJ, Marunick MT, Johns R. Malignant ameloblastoma, spindle cell variant. Arch Pathol Lab Med 2003;127(3):352-5. 6. Dhir K, Scuibba J, Tufano RP. Ameloblastic carcinoma of the maxilla. Oral Oncol 2003;39(7):736-41. 7. Avon SL, Mccomb J, Clokie C. Ameloblastic carcinoma: case report and literature review. J Can Dent Assoc 2003;69(9):573-6. 8. Cox DP, Muller S, Carlson GW, Murray D. Ameloblastic carcinoma ex ameloblastoma of the mandible with malignancy-associated hypercalcemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90(6):716-22. 9. Hamakawa H, Kayahara H, Sumida T, Tanioka H. Mandibular intraosseous carcinoma coexisting with ameloblastoma. J Oral Maxillofac Surg 2000;58(4):430-3. 10. Braunstein E, Vered M, Taicher S, Buchner A. Clear cell odontogenic carcinoma and clear cell ameloblastoma: a single clinicopathologic entity? A new case and comparative analysis of the literature. J Oral Maxillofac Surg 2003;61(9):1004-10. 11. Raubenheimer EJ, Van Heerden WFP, Noffke CEE. Infrequent clinicopathological findings in 108 ameloblastomas. J Oral Pathol Med 1995;24:227-32. 12. Van Rensburg LJ, Thompson IO, Kruger HE, Norval EJ. Hemangiomatous ameloblastoma: clinical, radiologic, and patho-
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Reprint requests: Erich J. Raubenheimer, MChD, PhD Department of Oral Pathology University of Limpopo Box D24 Medunsa, 0204, South Africa [email protected]